# Lipinski's Rule of 5 Oxygen Rules

I would like clarification on the role of oxygen as a hydrogen bond acceptor in Lipinski's Rule of 5 (for drug absorption). I have learned in my medicinal chemistry class that both electron pairs from an oxygen atoms are able to individually form hydrogen bonds.

I was wondering if every sp3 hybridized oxygen would account for 2 possible hydrogen bond acceptors in this rule for drug absorption? If not, what other mechanisms or in vivo findings are not causing oxygen to not count as double?

Too many hydrogen bond acceptor groups also hinder permeability across a membrane bi-layer. The sum of $\ce{N}$s and $\ce{O}$s is a rough measure of H bond accepting ability.